T-T COLLABORATION IN THE REJECTION OF ISLET ALLOGRAFTS

培养的同种异体胰岛簇移植物放置于 免疫活性异基因受者的肾胶囊 主要组织相容性复合体(MHC)的供体。如果满足以下条件，则发生拒绝 受者被注射了来自同基因捐赠者的T细胞。 先前已接种给移植物淋巴样细胞的受者 供体单倍型。来自正常、未被激发的供者的T细胞不能诱导 拒绝。消除T细胞的细胞毒/抑制亚群 废止的拒绝。这一结果的一个结论是细胞毒性T细胞 在该动物模型中，淋巴细胞(CTL)是移植物排斥反应所必需的。 系统。 该项目的目标是确定CTL是否足够或是否 需要与其他T细胞亚群合作。 要检验的假设是针对I类MHC的CTL 培养的同种异体胰岛移植物的同种抗原需要帮助，最有可能的是 IL-2的形式，来自针对I类MHC抗原的辅助性T细胞 (第I类特定帮助者)和脱落的移植物同种异体抗原 移植受者MHC(生理帮助者)的背景。 在该建议中，体内分离程序(阴性选择)是 描述。在否定选择的情况下，所提供的数据表明它应该 可以通过功能将CTL与I类特定的和 生理学帮手。提供的数据还将表明，消除， 通过负选择，所有三个子集的能力取消 剩余的T细胞来诱导排斥反应。通过适当的选择 程序，在正文中详细描述，将有可能 确定CTL亚群是单独还是与其他T细胞协同 亚群可诱导移植物排斥反应。这项研究，它唯一地确定了 T细胞亚群的功能和特异性，应该提供有用的 关于T细胞介导的机制的一般问题的信息 移植物排斥反应。

Cultured islet cluster allografts were not rejected when placed under the kidney capsule of immunocompetent allogeneic recipients differing from the donor at the major histocompatibility complex (MHC). Rejection occurred if the recipients were injected with T cells from donors syngeneic to the recipient who had been previously primed to lymphoid cells of the graft donor haplotype. T cells from normal, unprimed donors did not induce rejection. Elimination of the cytotoxic/suppressor subset of T cells abrogated rejection. One conclusion of this result is that cytotoxic T lymphocytes (CTL) are necessary for graft rejection in this animal model system. The aim of the project is to determine whether the CTL are sufficient or if collaboration with other T cell subsets is required. The hypothesis to be tested is that CTL specific for the class I MHC alloantigens of the cultured islet allograft require help, most likely in the form of IL-2, from helper T cells specific for class I MHC antigens (class I specific helpers) and shed graft alloantigens represented in the context of the graft recipients MHC (physiologic helper). In this proposal an in vivo separation procedure (negative selection) is described. With negative selection the data presented show that it should be possible to distinguish, by function, CTL from class I specific and physiologic helpers. The data presented also will show that elimination, via negative selection, of all three subsets abolishes the capacity of the remaining T cells to induce rejection. By appropriate selection procedures, described in detail in the text, it will be possible to determine if the CTL subset by itself or in collaboration with other T cell subsets can induce graft rejection. This study, which uniquely identifies T cell subsets by function and specificity, should provide useful information on the general question of the mechanism of T cell mediated graft rejection.